Translation of the cell adhesion molecule ALCAM in axonal growth cones - regulation and functional importance
Translation of the cell adhesion molecule ALCAM in axonal growth cones - regulation and functional importance
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DOI：
10.1242/jcs.096149
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发表时间：
2012-02-15
影响因子：
4
通讯作者：
Pollerberg, G. Elisabeth
中科院分区：
文献类型：
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作者：
Thelen, Karsten;Maier, Bettina;Pollerberg, G. Elisabeth
ALCAM是一种存在于延伸轴突上的细胞粘附分子，并且已被证明对于视网膜神经节细胞（RGC）轴突的延伸和导航至关重要。在本研究中，我们表明，ALCAM mRNA存在于轴突生长锥的RGCs在体内和体外，ALCAM的翻译发生在RGC生长锥分离其索马。这种生长锥翻译由ALCAM的3 '-非翻译区（3'-UTR）调节，并取决于激酶ERK和TOR（雷帕霉素的靶标）的活性。我们还研究了ALCAM的生长锥翻译对轴突功能的影响。ALCAM的生长锥翻译对于与ALCAM蛋白接触延伸的轴突的增强伸长至关重要。ALCAM在生长锥中的局部翻译能够快速平衡实验诱导的ALCAM内化，从而有助于维持质膜中恒定的ALCAM水平。RGC轴突可以选择在层粘连蛋白或ALCAM和层粘连蛋白两者上生长的测定-如发育中的视网膜中的情况-揭示了轴突对含有ALCAM的泳道的偏好取决于生长锥中ALCAM的翻译。总之，这些结果首次显示了生长锥中细胞粘附分子的翻译，以及这种局部翻译对轴突和生长锥行为的影响。
ALCAM is a cell adhesion molecule that is present on extending axons and has been shown to be crucial for elongation and navigation of retinal ganglion cell (RGC) axons. In the present study, we show that ALCAM mRNA is present in axonal growth cones of RGCs in vivo and in vitro, and that translation of ALCAM occurs in RGC growth cones separated from their soma. This growth cone translation is regulated by the 3'-untranslated region (3'-UTR) of ALCAM and depends on the activity of the kinases ERK and TOR (target of rapamycin). We also investigated the impact of the growth cone translation of ALCAM on axonal functions. Growth cone translation of ALCAM is crucial for the enhanced elongation of axons extending in contact with ALCAM protein. The local translation of ALCAM in the growth cone is able to rapidly counterbalance experimentally induced ALCAM internalization, thereby contributing to the maintenance of constant ALCAM levels in the plasma membrane. Assays where RGC axons have the choice to grow on laminin or both ALCAM and laminin - as is the case in the developing retina - reveal that the axonal preference for ALCAM-containing lanes depends on translation of ALCAM in growth cones. Taken together, these results show for the first time that translation of a cell adhesion molecule in growth cones, as well as the impact of this local translation on the behavior of axon and growth cone.